tbuckley/cabot-search huggingface dataset:
47P Prognostic value of dynamic HER2 status conversion in patients with metastatic breast cancer: Retrospective study of the Clinic of Medical Oncology of Military Medical Academy, Sofia, Bulgaria
Authors: A.L. Garev, D. Petkova-Nelova, Z. Mihaylova, V. Hadjiiska, A. Fakirova
Journal: Annals of Oncology (2022)
4MO Multi-focal genomic dissection of synchronous primary and metastatic tissue from de novo metastatic prostate cancer
Authors: A.J. Murtha, E. Warner, K. van der Eecken, E. Kwan, C. Herberts, J. Sipola, S. Ng, E. Chen, N. Fonseca, E. Schönlau, C. Bernales, G. Donnellan, S. Verbeke, N. Lumen, J. van Dorpe, B. De Laere, M. Annala, G. Vandekerkhove, P. Ost, A.W. Wyatt
Journal: Annals of Oncology (2022)
40P The detection and quantification of different sequence-variable NPM1 mutations using RNase H-dependent PCR (rhPCR)
Authors: G. Gaina, D. Soare, I.M. Lambrescu, V. Ionescu, A. Popa, O. Mosoia, M. Pavalean, L. Ceafalan, V. Cismasiu
Journal: Annals of Oncology (2022)
9P Small-scale ROS1 aberrations: Functional impact and therapeutic potential
Authors: M. Glaser, C. von Levetzow, S. Michels, L. Nogova, M. Katzenmeier, C. Wömpner, J. Schmitz, E. Bitter, I. Terjung, E. Passmann, D. Schaufler, A. Eisert, R.N. Fischer, R. Riedel, S. Hahne, S. Merkelbach-Bruse, R. Büttner, J. Wolf, M. Scheffler
Journal: Annals of Oncology (2022)
44P Prognostic value of androgen receptor expression in premenopausal women with estrogen receptor-positive breast cancer
Authors: H.C. Yildirim, M. Üner, T. Yildiran, D.C. Guven, F. Yilmaz, S. Yasar, Y.N. Evlendi, O. Dizdar, A. Üner, S. Aksoy
Journal: Annals of Oncology (2022)
25P Differential response to platinum agents of patients carrying the germline BRCA1 c.211 A&gt;G pathogenic variant
Authors: M.I. Gomez-Randulfe Rodriguez, S. Silva Díaz, R. Lesta Mellid, M. Quindos Varela, B. Alonso de Castro, I. Parajó Vázquez, R. Garcia Campelo
Journal: Annals of Oncology (2022)
29P Sarcoma patients need precision oncology: Is molecular tumor board the right way?
Authors: A. Cosimati, C.E. Onesti, F. Salvatori, F. Riva, S. Vari, D. Renna, D. Buccilli, R. Covello, B. Casini, F. Rollo, G. Ciliberto, V. Ferraresi
Journal: Annals of Oncology (2022)
45P In silico transcriptomic mapping of Notch biological pathway in luminal breast cancer
Authors: K.I. Rojas Laimito, M.R. Martin, F. Rojo, A. Gámez-Pozo, F.J. De Castro, E. Filipovich Vegas, J. Ceballos Viro, J.E. Ales Martínez
Journal: Annals of Oncology (2022)
42P Independent prognostic value of flow cytometry (FCM) in myelodysplastic syndromes (MDS): Composition of a prognostic FCM-score for overall survival
Authors: A. Santaolalla, U. Oelschlaegel, J. Timms, S. Winter, P. Parker, C.N. Harrison, T.M. Westers, A.A. van de Loosdrecht, M. van Hemelrijck, U. Platzbecker, S. Kordasti
Journal: Annals of Oncology (2022)
6MO Pan-cancer characterization of receptor tyrosine kinases alterations to sort targetable drivers from passengers
Authors: H. Vanacker, V.K. Attignon, M. Brahmi, A. Dufresne, P. Cassier, M. Carbonnaux, D. Pissaloux, S. Boyault, Q.L. Wang, O. Tredan, F. Tirode, J-Y. Blay
Journal: Annals of Oncology (2022)
31P Liquid biopsies in clinical practice
Authors: D. Repana, T. Shanmugalingam, G. Gerrard, N. Foot, A. Kulkarni, K. Naidoo, S. Talukdar, K. Snape, H. Hanson, K. Quigley, K. Mokretar, P. Du Parcq, B. Ferguson, D. Sarker, N. Murugaesu
Journal: Annals of Oncology (2022)
3MO Genomic evolution of non-small cell lung cancer during the establishment and propagation of patient-derived xenograft models
Authors: R. Hynds, A. Huebner, D. Pearce, O. Pich, A. Akarca, D. Moore, S. Ward, M. Hill, M. Jamal-Hanjani, T. Marafioti, N. McGranahan, C. Swanton
Journal: Annals of Oncology (2022)
50P Transcriptomic profiles of CD32b in breast cancer predict outcome and are associated with immune activation
Authors: K.I. Rojas Laimito, M. Vieito Villar, V. Galvao de Aguiar, O. Saavedra Santa Gadea, M.J. Lostes Bardaji, A. Oberoi, G. Alonso, I. Brana, J. Tabernero, E. Garralda
Journal: Annals of Oncology (2022)
92P Selective elimination of CD133+ cancer stem cells using novel BET/HDAC inhibitor TW09 as therapy for pancreatic ductal adenocarcinoma (PDAC)
Authors: K. Tiwary, S. Mader, S. Hauff, A. Valar, T. Ditrich, X. Zhang, A. Kleger, T. Seufferlein, B. Sanz, J. Siveke, K. Walter, P.C. Hermann
Journal: Annals of Oncology (2022)
5MO Hypomethylation of circulating retrotransposons: Towards a non-invasive pan-cancer diagnosis
Authors: C. Proudhon, M. Michel, M. Heidary, A. Mechri, C. Hego, A. Rampanou, C. Le Tourneau, M. Kamal, B. Ivan, M-H. Stern, O. Lantz, L. Cabel, J-Y. Pierga, F.C. Bidard, C-A. Azencott
Journal: Annals of Oncology (2022)
72P Liquid biopsy biomarkers utility in radiation oncology
Authors: G.A. Cifuentes, L. Mendez, A. Santiago, M. Fueyo, E. López Martínez, R. Soria, N. Durán, R. Álvarez, M. Diñeiro, R. Capín, J. Cadiñanos, R. Cabanillas Farpón
Journal: Annals of Oncology (2022)
121P ATM germline mutations in lethal prostate cancer
Authors: R.M. Grochot, S. Carreira, S. Miranda, I. Figueiredo, C. Bertan, J. Rekowski, W. Yuan, A. Ferreira, R. Riisnaes, A. Neeb, B. Gurel, M.D.L.D. Fenor de la Maza, J. Carmichael, D. Westaby, C. Guo, A. Sharp, J.S. de Bono
Journal: Annals of Oncology (2022)
55P Comparison of BiomeOne and PD-L1 expression tests as a predictor for response to immune checkpoint inhibitors (ICI) in patients with non-small cell lung cancer (NSCLC)
Authors: I. Robinson, M.J. Hochmair, L. Ay, G. Absenger, C. Jansen, C. Pacifico, B. Sladek, A. Knabl, N. Gasche, A. Valipour
Journal: Annals of Oncology (2022)
99P The transcriptional atlas of co-targeted PIM/PI3K/mTOR ex-vivo patient-derived prostate cancer as revealed by spatial transcriptomics
Authors: U.A. Okoli, G. Akman, V. Thavarajah, L.M. Carmona Echeverria, J. Griffin, R. Ohayi, A. Freeman, A. Haider, G. Shaw, A.N. Sridhar, J. Kelly, B. Simpson, H. Pye, J. Crompton, H. Whitaker, U. Cheema, S. Heavey
Journal: Annals of Oncology (2022)
1MO Air pollution-induced non-small cell lung cancer: Towards molecular cancer prevention
Authors: E. Lim, W. Hill, C. Lee, C.E. Weeden, M. Augustine, K. Chen, F.C. Kuan, F. Marongiu, E. Evans, D. Moore, M.H. Ryu, M. Luchtenborg, K. Lavelle, C. Carlsten, I. Malanchi, A. Hackshaw, K.R. Litchfield, J. Degregori, M. Jamal-Hanjani, C. Swanton
Journal: Annals of Oncology (2022)
34P Gustave Roussy Match-R study: A descriptive analysis of the molecular target population
Authors: J.D. Florez Arango, J.E. Rodriguez, F. Facchinetti, G. Guaitoli, J.C. Benitez Montanez, C. Baldini, J-Y. Scoazec, L. Lacroix, D. Vasseur, J-C. Soria, Y. Loriot, F. André, L. Friboulet, B. Besse, S. Ponce
Journal: Annals of Oncology (2022)
129P Molecular screening and early phase trial inclusion for head and neck squamous cell carcinoma patients
Authors: A. Vozy, C. Roussel-Simonin, A. Houessinon, A. Bayle, F. Blanc-Durand, F.R. Ferrand, A. Fouilloux, M. Iacob, N. Khalife, S. Ponce, Y. Loriot, C. Baldini, A. Italiano, C. Even
Journal: Annals of Oncology (2022)
64P Integrative immune transcriptomic classification could improve patient selection for precision immunotherapy in advanced gastroesophageal adenocarcinoma
Authors: M. Cabeza Segura, V. Gambardella, F. Gimeno-Valiente, J.A. Carbonell-Asins, L. Alarcon-Molero, A. Gonzalez-Vilanova, S. Zuniga-Trejos, P. Rentero-Garrido, R. Villagrasa, M. Gil Raga, P. Richart, M. Huerta, S. Rosello Keranen, D. Roda Perez, N. Tarazona Llavero, C. Martínez-Ciarpaglini, J. Castillo, A. Cervantes, T.C. Fleitas
Journal: Annals of Oncology (2022)
138P Dissecting intra-tumoral heterogeneity in localized HR+/Her2− breast cancer using single cell DNA sequencing
Authors: L. Cerbone, D.T.N. Tran, A. Tran Dien, B. Verret, N. Droin, V. Scott, I.J. Garberis, A. Savaudet, F. Maella, B. Leite, J-Y. Scoazec, C. Ayadi, C. Machavoine, V. Camara-Clayette, F. André
Journal: Annals of Oncology (2022)
137P Combining protein and mRNA spatial profiles to identify distinct cell population in metaplastic breast cancer
Authors: H. Kuasne, P. Savage, B. Khadang, J. Lai, C. Martinez Ramirez, A. Monast, A-M. Fortier, S. Busque, J. Asselah, N. Bouganim, S. Meterissian, A. Omeroglu, M. Basik, Y. Riazalhosseini, M. Park
Journal: Annals of Oncology (2022)
48P The relationship among bowel FDG-PET uptake, pathological complete response, and the influence of eating and exercise habits in breast cancer patients undergoing neoadjuvant chemotherapy
Authors: P. Tiberio, L. Antunovic, M. Gaudio, A. Viganò, M. Pastore, C. Miggiano, F. Jacobs, C. Benvenuti, E. Farina, A. Chiti, A. Santoro, R. De Sanctis
Journal: Annals of Oncology (2022)
84P Autologous ECM-composed scaffolds and zebrafish PDXs for individualized theranostics in rare neuroendocrine neoplasms
Authors: C. Calabrese, G. Miserocchi, S. Vanni, C. Spadazzi, A. De Vita, C. Cocchi, A. Bongiovanni, N. Ranallo, F. Pieri, G.L. Frassineti, M. Tebaldi, F. Foca, G. Ercolani, D. Cavaliere, C.A. Pacilio, L. Mercatali, C. Liverani
Journal: Annals of Oncology (2022)
43P High intratumoral density of double-positive CD8/GRMZ lymphocytes, BRCAness and elevated TAP2 expression are predictive for improved breast cancer (BC) response to neoadjuvant chemotherapy (NACT)
Authors: E.S. Kuligina, A.O. Ivantsov, A. Martianov, Y. Gorgul, A.R. Venina, S.V. Baskina, E.N. Imyanitov
Journal: Annals of Oncology (2022)
134P Whole transcriptome RNA-Seq analysis of formalin-fixed and paraffin-embedded tumour tissue
Authors: N. Hajkova, E. Krkavcová, R. Michalkova, J. Dvořák, J. Hojný, M. Bártů, I. Stružinská, K. Nemejcova, P. Dundr
Journal: Annals of Oncology (2022)
80P Dual cell cycle arrest in KRAS mutant cell lines by co-inhibition of MAPK and Hippo-YAP1 pathways
Authors: S.L. Tammaccaro, P. Prigent, J.C. Le Bail, O. Dos Santos, L. Dassencourt, P. Picard-Vernier, M. Eskandar, A. Buzy, J-C. Guillemot, Y. Veeranagouda, M. Didier, E. Spanakis, T. Kanno, M. Cesaroni, S. Mathieu, L. Canard, A.H. Casse, L. Debussche, J. Moll, I. Valtingojer
Journal: Annals of Oncology (2022)
136P Paths of chromosomal instability and copy number alteration in circulating tumor cells of progressing early-stage breast cancer patients
Authors: M. Silvestri, C. Reduzzi, M. Vismara, M. Valenti, S. Folli, M. Cristofanilli, G. Pruneri, S. Di Cosimo, V. Cappelletti
Journal: Annals of Oncology (2022)
81P Effect of disulfide bonds and N-glycosylation on the recognition of the NaPi2b transporter by monoclonal antibodies
Authors: D. Reshetnikova, L.F. Bulatova, V. Skripova, D. Savenkova, A.K. Nurgalieva, M. Bogdanov, R. Kiyamova
Journal: Annals of Oncology (2022)
127P RAS, RAF and NF1 oncogenic mutations in KRAS-mutated lung adenocarcinoma
Authors: D. Marinelli, S. Pisegna, A. Chiavassa, E. Bengala, C. Capasso, A. Sabatini, F. Ciurluini, A. Artemi, A. Torchia, F.T. Gallina, A. Botticelli, P. Gazzaniga, E. Cortesi, A.J. Gelibter
Journal: Annals of Oncology (2022)
110P Clinical validation of a 50-gene hotspot NGS panel in Asian patients with solid tumors
Authors: D. Lim, S. Teo, Y.L. Toh, C.W. Law, J. Wong, X.W. Yau, Z.W. Wong, Y. Li, C.K. Tan, M. Chan, S.Y. Tan
Journal: Annals of Oncology (2022)
46P The impact of antibiotics and proton pump inhibitors in neoadjuvant treatment of HER2+ breast cancer
Authors: J.B. Martins, J. Santos, J.C. Mendonca, A.R. Barbosa, B.F. Lima, C.T. Carvalho, A. Teixeira, C. Coutinho
Journal: Annals of Oncology (2022)
103P The effect of carboplatin on sodium-dependent phosphate transporter NaPi2b expression in the OVCAR-4 ovarian cancer cell line
Authors: A.K. Nurgalieva, I. Khalitova, V. Skripova, V. Popov, S. Safina, E. Shakirova, R. Kiyamova
Journal: Annals of Oncology (2022)
147TiP Exactis-01 - Clinical utility of returning liquid biopsy NGS results in NSCL cancer patients: A Canadian trial through the Exactis Network
Authors: M. Marques, K. Gambaro, A. Hébert-Losier, S. McNamara, G. Batist, N. Leighl, J. Agulnik
Journal: Annals of Oncology (2022)
128P Precision genomics based targeted 12 gene biomarker and PD-L1 testing in advanced non-small cell lung cancer patients as an alternative to conventional EGFR, ALK, ROS-1 sequential testing in a tertiary care hospital
Authors: M. Nagaraj, S. Patil, R. Thippeswamy, S. Chiradoni Thungappa
Journal: Annals of Oncology (2022)
11P Mapping the pattern and pace of tumour dissemination using longitudinal imaging and ctDNA in the TRACERx lung study
Authors: W.K. Liu, B. Ding, S. Hessey, J. Kittel, C. Lombardelli, H. Lee, C. Veiga, A. Huebner, A. Hackshaw, C.Z. Abbosh, A.M. Frankell, G. Royle, C. Swanton, M. Jamal-Hanjani
Journal: Annals of Oncology (2022)
95P Organoid sensitivity for panitumumab based on primary tumor location and mutational status
Authors: L.P. Smabers, E. Wensink, C.S. Verissimo, E. Koedoot, K-C. Pitsa, M. Huismans, C. Higuera Barón, R. Korporaal, E. Teal, L. Valkenburg-van Iersel, G.A. Cirkel, A. Brousali, R. Overmeer, M. Braat, S. Elias, R. Vries, O. Kranenburg, M. Koopman, S. Boj, J. Roodhart
Journal: Annals of Oncology (2022)
106P Ultra low-coverage whole genome sequencing for precision oncology in solid tumors
Authors: T.S. Tarawneh, F. Rodepeter, P. Ross, J. Teply-Szymanski, V. Koch, C. Thölken, J. Riera Knorrenschild, T. Wündisch, C. Denkert, A. Neubauer, E. Mack
Journal: Annals of Oncology (2022)
145P Everolimus for the treatment of thymic epithelial tumors (TETs): A real-world experience
Authors: J.D. Florez Arango, J.C. Benitez Montanez, A. Botticella, M. Aldea, C. Le Pechoux, A.M. Grecea, A. Levy, C. Roux, M. Frelaut, S. Mussot, O. Mercier, E. Fadel, J-Y. Scoazec, D. Planchard, F. Barlesi, B. Besse
Journal: Annals of Oncology (2022)
109P Characteristics of clonal hematopoiesis-related mutations identified in liquid biopsies from patients with metastatic solid tumors
Authors: D. Vasseur, A. Arbab, F. Giudici, C. Marzac, S. Michiels, M. Tagliamento, A. Bayle, M. Aldea, A. Fievet, N. Auger, L. Friboulet, F. Facchinetti, A. Géraud, S. Ponce, A. Hollebecque, B. Besse, J. Baptiste Micol, A. Italiano, L. Lacroix, E. Rouleau
Journal: Annals of Oncology (2022)
141P Comprehensive genomic profiling-based precision oncology in the management of rare paediatric soft tissue sarcomas
Authors: C. Cervi, G. Bedics, O. Brzon, L. Kotmayer, Z. Sápi, E. Zajta, L. Hegyi, J. Pápay, K. Dezső, E. Varga, L. Felkai, R. Bánusz, C. Bödör, M. Csóka
Journal: Annals of Oncology (2022)
132P Genomic profiling of primary and recurrent ovarian cancers: A retrospective single-center experience
Authors: E. Giudice, V. Ghizzoni, M.V. Carbone, S. Cappuccio, V. Salutari, L. Musacchio, C. Nero, C. Ricci, F. Camarda, M.T. Perri, D. Giannarelli, A. Fagotti, G. Scambia, D. Lorusso
Journal: Annals of Oncology (2022)
75P Biosynthesis and characterization of selenium nanoparticles using marine algae Sargassum wightii: Understanding its anticancer activity through ROS-mediated p53 and Akt signaling pathways in A549 cells
Authors: C. Loganathan, P. Sakayanathan, P. Sathishkumar, P. Thayumanavan
Journal: Annals of Oncology (2022)
120P The compartment-specific spatial transcriptomic landscape of 3D cultured Gleason 7 prostate cancer
Authors: V. Thavarajah, G. Akman, L.M. Carmona Echeverria, J. Griffin, A. Freeman, A. Haider, G. Shaw, A. Narashima Sridhar, J. Kelly, H. Pye, J. Crompton, A. Enica, H. Whitaker, U.A. Okoli, U. Cheema, S. Heavey
Journal: Annals of Oncology (2022)
144P Development of a 6-color multiplex crystal digital PCR assay for the simultaneous detection of ESR1 and PIK3CA mutations in the plasma of metastatic breast cancer patients
Authors: J. Corné, V. Quillien, F. Godey, F. Le Du, L. Robert, H. Bourien, A. Brunot, L. Crouzet, C. Perrin, C. Lefeuvre-Plesse, V.C. Dieras, T. De La Motte Rouge
Journal: Annals of Oncology (2022)
112P Clinicopathological characterization of MTAP-altered metastatic gastrointestinal tumors
Authors: G. Mauri, G. Patelli, L. Roazzi, A. Amatu, G. Calvanese, F. Martinelli, G. Marrapese, E.F. Bonazzina, F.M. Tosi, K. Bencardino, A. Bardelli, S. Siena, A. Sartore Bianchi
Journal: Annals of Oncology (2022)
126P Clonal architecture and genomic features of smoking versus non-smoking oncogene-driven East-Asian non-small cell lung cancer
Authors: C-Y. Huang, N. Jiang, M. Shen, G. Lai, A. Takano, T.K.H. Lim, W.L. Tam, A. Skanderup, D.S.W. Tan, S.G. Rozen
Journal: Annals of Oncology (2022)
124P Feasibility of multidisciplinary translational CAPRICE project: Study protocol and workflow
Authors: E.R. Mendez Carrascosa, E.C. Vera, D. Aldave, A. Sánchez, C. Velasco, E. Castro Marcos, D. Olmos, A. Zapatero, L.A. San José, N. Romero Laorden
Journal: Annals of Oncology (2022)
Normalization and de-noising of single-cell Hi-C data with BandNorm and scVI-3D
Authors: Ye Zheng, Siqi Shen, Sündüz Keleş
Journal: Genome biology (2022)

Single-cell high-throughput chromatin conformation capture methodologies (scHi-C) enable profiling of long-range genomic interactions. However, data from these technologies are prone to technical noise and biases that hinder downstream analysis. We develop a normalization approach, BandNorm, and a deep generative modeling framework, scVI-3D, to account for scHi-C specific biases. In benchmarking experiments, BandNorm yields leading performances in a time and memory efficient manner for cell-type separation, identification of interacting loci, and recovery of cell-type relationships, while scVI-3D exhibits advantages for rare cell types and under high sparsity scenarios. Application of BandNorm coupled with gene-associating domain analysis reveals scRNA-seq validated sub-cell type identification.
A quantitative metric of pioneer activity reveals that HNF4A has stronger in vivo pioneer activity than FOXA1
Authors: Jeffrey L. Hansen, Barak A. Cohen
Journal: Genome biology (2022)

Abstract Background We and others have suggested that pioneer activity — a transcription factor’s (TF’s) ability to bind and open inaccessible loci — is not a qualitative trait limited to a select class of pioneer TFs. We hypothesize that most TFs display pioneering activity that depends on the TF concentration and the motif content at their target loci. Results Here, we present a quantitative in vivo measure of pioneer activity that captures the relative difference in a TF’s ability to bind accessible versus inaccessible DNA. The metric is based on experiments that use CUT&amp;Tag to measure the binding of doxycycline-inducible TFs. For each location across the genome, we determine the concentration of doxycycline required for a TF to reach half-maximal occupancy; lower concentrations reflect higher affinity. We propose that the relative difference in a TF’s affinity between ATAC-seq labeled accessible and inaccessible binding sites is a measure of its pioneer activity. We estimate binding affinities at tens of thousands of genomic loci for the endodermal TFs FOXA1 and HNF4A and show that HNF4A has stronger pioneer activity than FOXA1. We show that both FOXA1 and HNF4A display higher binding affinity at inaccessible sites with more copies of their respective motifs. The quantitative analysis of binding suggests different modes of binding for FOXA1, including an anti-cooperative mode of binding at certain accessible loci. Conclusions Our results suggest that relative binding affinities are reasonable measures of pioneer activity and support the model wherein most TFs have some degree of context-dependent pioneer activity.
scGWAS: landscape of trait-cell type associations by integrating single-cell transcriptomics-wide and genome-wide association studies
Authors: Peilin Jia, Ruifeng Hu, Fangfang Yan, Yulin Dai, Zhongming Zhao
Journal: Genome biology (2022)

Abstract Background The rapid accumulation of single-cell RNA sequencing (scRNA-seq) data presents unique opportunities to decode the genetically mediated cell-type specificity in complex diseases. Here, we develop a new method, scGWAS, which effectively leverages scRNA-seq data to achieve two goals: (1) to infer the cell types in which the disease-associated genes manifest and (2) to construct cellular modules which imply disease-specific activation of different processes. Results scGWAS only utilizes the average gene expression for each cell type followed by virtual search processes to construct the null distributions of module scores, making it scalable to large scRNA-seq datasets. We demonstrated scGWAS in 40 genome-wide association studies (GWAS) datasets (average sample size N ≈ 154,000) using 18 scRNA-seq datasets from nine major human/mouse tissues (totaling 1.08 million cells) and identified 2533 trait and cell-type associations, each with significant modules for further investigation. The module genes were validated using disease or clinically annotated references from ClinVar, OMIM, and pLI variants. Conclusions We showed that the trait-cell type associations identified by scGWAS, while generally constrained to trait-tissue associations, could recapitulate many well-studied relationships and also reveal novel relationships, providing insights into the unsolved trait-tissue associations. Moreover, in each specific cell type, the associations with different traits were often mediated by different sets of risk genes, implying disease-specific activation of driving processes. In summary, scGWAS is a powerful tool for exploring the genetic basis of complex diseases at the cell type level using single-cell expression data.
Global early replication disrupts gene expression and chromatin conformation in a single cell cycle
Authors: Miguel M. Santos, Mark C. Johnson, Lukáš Fiedler, Philip Zegerman
Journal: Genome biology (2022)

Abstract Background The early embryonic divisions of many organisms, including fish, flies, and frogs, are characterized by a very rapid S-phase caused by high rates of replication initiation. In somatic cells, S-phase is much longer due to both a reduction in the total number of initiation events and the imposition of a temporal order of origin activation. The physiological importance of changes in the rate and timing of replication initiation in S-phase remains unclear. Results Here we assess the importance of the temporal control of replication initiation using a conditional system in budding yeast to drive the early replication of the majority of origins in a single cell cycle. We show that global early replication disrupts the expression of over a quarter of all genes. By deleting individual origins, we show that delaying replication is sufficient to restore normal gene expression, directly implicating origin firing control in this regulation. Global early replication disrupts nucleosome positioning and transcription factor binding during S-phase, suggesting that the rate of S-phase is important to regulate the chromatin landscape. Conclusions Together, these data provide new insight into the role of the temporal control of origin firing during S-phase for coordinating replication, gene expression, and chromatin establishment as occurs in the early embryo.
The health and social care crisis makes tobacco control an imperative
Authors: Nick Hopkinson
Journal: BMJ (2022)

Carcinosarcoma is a rare neoplasm which, in the female genital tract, arises mainly in the endometrium. Although the pathogenesis remains obscure, there is an apparent association between pelvic irradiation and uterine sarcomas. There have been sporadic case reports of the development of carcinosarcomas of the cervix, vagina, and extragenital areas, but not of the ovary, after previous pelvic irradiation. We describe a case of ovarian carcinosarcoma arising in a 74-year-old female who had pelvic irradiation 33 years previously. Exploratory laparotomy showed a 25 × 18 × 9 cm left ovarian tumor with adjacent organ invasion including periuterine serosa and rectum. The patient was treated by optimal cytoreduction, followed by chemotherapy with adriamycin and cisplatin. However, acute hepatitis caused by reactivation of hepatitis B virus infection developed just before the fifth course of chemotherapy. She died of hepatic failure two weeks later.
DICER1 Mutations Occur in More Than One-Third of Follicular-Patterned Pediatric Papillary Thyroid Carcinomas and Correlate with a Low-Risk Disease and Female Gender Predilection
Authors: Semen Onder, Ozgur Mete, Ismail Yilmaz, Aysel Bayram, Sidar Bagbudar, Ali Yılmaz Altay, Gizem Issin, Neslihan Kaya Terzi, Yalın Iscan, Ismail Cem Sormaz, Fatih Tunca, Yasemin Giles Senyurek, Gulcin Yegen
Journal: Endocrine Pathology (2022)